Effects of enzyme replacement therapy on pain and health related quality of life in patients with Fabry disease: data from FOS (Fabry Outcome Survey)

Background: Fabry disease is an X linked lysosomal storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A. This leads to accumulation of globotriaosylceramide in nearly all tissues, including the blood vessels, kidney, myocardium, and nervous system. Symptoms often begin in childhood and include acroparaesthesia, with burning or tingling pain that spreads from the extremities to more proximal sites.

Aims: This study set out to evaluate pain and its influence on quality of life in patients with Fabry disease receiving enzyme replacement therapy (ERT) with agalsidase alfa.

Methods: Data were obtained from the Fabry Outcome Survey. Pain was measured using the Brief Pain Inventory (BPI), and health-related quality of life (HRQoL) was documented with the European Quality of Life Questionnaire (EQ-5D).

Results: The mean (SD) score for "pain at its worst" on the BPI prior to ERT was 5.1 (2.7). One year after commencement of ERT, this had improved by 0.5, and improved by a further 0.6 after 2 years (p<0.05). Similar statistically significant improvements were seen for "pain on average" and "pain now" after 2 years of ERT. The mean HRQoL utility score prior to ERT was 0.66 (0.32). After 12 months of treatment with agalsidase alfa, this had improved to 0.74 (0.26; p<0.05); this improvement was maintained after 2 years.

Conclusions: ERT with agalsidase alfa significantly reduces pain and improves quality of life in patients with Fabry disease.

     

Evolution of age at menarche and at onset of regular cycling in a large cohort of French women

BACKGROUND: Early exposure to ovarian hormones is considered to increase breast cancer incidence. The age at which the ovaries become functional is thus important. METHODS: We explored the evolution of age at first menstruation and at onset of regular cycling in 86 031 women participating in the E3N-EPIC cohort study, part of the European Prospective Investigation into Cancer. RESULTS: We observed an increase in mean age at menarche among women born between 1925 and 1930, followed by a steady decrease in the youngest birth cohorts. In contrast, age at onset of regular cycling increased gradually from 1925 onwards. There was thus a steady increase in the interval between age at menarche and at onset of regular cycling, mainly due to an increase in the percentage of women in whom regular cycling started at least 5 years after menarche (from 9.0% among women born in 1925-1929 to 20.8% in those born in 1945-1950). The increase in the interval between menarche and onset of regular cycling was even greater among women with a late menarche. CONCLUSIONS: This increase might be due to a change in dietary intake and/or physical exercise aimed at achieving the slim silhouette desired by the younger generations.     

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low-risk (0–3), medium-risk (4–5), and high-risk (6–10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.     

European multicenter study of natural family planning (1989–1995): efficacy and drop-out

Background: Effectiveness studies in natural family planning (NFP) published over the past 20 years have shown a wide range of contraceptive efficacy and acceptability. This seems to be due in part to different NFP methodologies. Consequently, we decided to carry out an effectiveness study in Europe to examine one group of the most widely spread NFP methods, the sympto-thermal methods.Methods: Between 1989 and 1995, 15 NFP groups from 10 European countries participated in a prospective European multicentre study. This paper reports on l328 women aged between 19 and 45 years and willing to participate for at least 12 cycles. Two types of symptothermal methods were mainly used, the symptothermal double-check methods (1046 women, 16 865 cycles of exposure, 34 unintended pregnancies) and the symptothermal single-check methods (214 women, 1495 cycles of exposure, 13 unintended pregnancies). The study was an observational study with prospectively collected data. The pregnancy rates, drop-out rates and lost-to-follow-up rates are presented separately for both subgroups according to the Kaplan–Meier method.Results: For the double-check methods, there was an unintended pregnancy rate of 2.6% at the end of the first 12 cycles of use (standard error or SE 0.55%), a drop-out rate for difficulties or dissatisfaction of 3.9% (SE 0.69%) and a lost-to-follow-up rate of 3.l% (SE 0.62%). In the single-check group, there was a total of 13 unintended pregnancies at the end of the first 12 cycles of study participation, giving an unintended pregnancy rate of 8.5% (SE 2.52%), a drop-out rate for difficulties or dissatisfaction of 3.0% (SE 1.76%) and a lost-to-follow-up rate of 23.4% (SE 4.35%). No pregnancy was observed in women over 40 years of age. Most pregnancies occurred because of deliberate unprotected intercourse in the fertile phase (user failure).Conclusions: The symptothermal double-check methods have proved to be effective family planning methods in Europe. The low drop-out-rate for difficulties or dissatisfaction with NFP shows the good acceptability.